Stem cell secretome offers a promising alternative to stem cell transplantation for treating myocardial infarction (MI). However, its clinical application faces two major challenges: how to enhance the levels of growth factors within the secretome to promote cardiac cell survival and vascularization, and how to efficiently deliver the secretome to the infarcted heart during the acute MI phase without risking rupture of the weakened myocardium. To address these challenges, we upregulated angiogenic growth factors in the secretome from adipose-derived stem cells (ADSC-secretome) by conditioning the cells under hypoxia and with insulin-like growth factor 1 (IGF-1). Our results show that exposure to 1 % O₂ condition significantly increased the expression of VEGF, bFGF, and PDGF-BB compared to 5 % O₂ condition. Co-treatment with IGF-1 further elevated the levels of these growth factors and, notably, reduced the secretion of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6 from the ADSCs. To rapidly and specifically deliver the secretome to the infarcted heart during acute MI, we encapsulated it within ischemia-targeting nanoparticles. These nanoparticles, designed for intravenous injection, preferentially accumulated in the infarcted region. The treatment significantly improved cardiac cell survival, tissue vascularization, and cardiac function. These findings suggest that ADSC secretome, enriched with angiogenic growth factors, holds strong potential for facilitating cardiac repair following MI.

Herbal medicine exhibits a broad spectrum of potent anti-cancer properties, including the enhancement of tumor immune responses, reversal of multidrug resistance, regulation of autophagy and ferroptosis, as well as anti-proliferative, pro-apoptotic, and anti-metastatic effects. This review systematically explores recent advances (primarily documented since 2019) in research on key anti-cancer compounds derived from herbal medicine, such as apigenin, artemisinin, berberine, curcumin, emodin, epigallocatechin gallate (EGCG), ginsenosides, icariin, resveratrol, silibinin, triptolide, and ursolic acid (UA). These studies were sourced from scientific databases, including PubMed, Web of Science, Medline, Scopus, and Clinical Trials. The review focuses on the significant role that these natural products play in modern oncology, exploring their efficacy, mechanisms of action, and the challenges and prospects of integrating them into conventional cancer therapies. Furthermore, it highlights cutting-edge approaches in cancer research, such as the utilization of gut microbiota, omics technologies, synthetic derivatives, and advanced drug delivery systems (DDS). This review underscores the potential of these natural products to advance the development of novel anti-cancer treatments and support contemporary medicine. Additionally, recent multi-omics findings reveal how these compounds reshape transcriptional and metabolic networks, further broadening their therapeutic scope. Many natural products exhibit synergy with first-line chemotherapies or targeted therapies, thereby enhancing treatment efficacy and reducing side effects. Advanced nano-formulations and antibody-drug conjugates have also substantially improved their bioavailability, making them promising candidates for future translational research.

Liver diseases, such as hepatitis, cirrhosis, and liver cancer, pose significant public health challenges, ranking as the twelfth leading cause of death globally. Given the liver's critical functions in metabolism, detoxification, and biosynthesis, its impairment can lead to severe consequences, often resulting in end-stage liver failure. Although liver transplantation is regarded as the definitive intervention for advanced liver disease, factors such as a shortage of donors and potential surgical complications necessitate the investigation of non-surgical regenerative medicine alternatives. This manuscript provides a comprehensive review of innovative non-surgical therapies aimed at liver regeneration, with an emphasis on both cell-based and cell-free approaches. It examines the contributions of various stem cell populations, including mesenchymal stem cells, hematopoietic stem cells, and induced pluripotent stem cells, in facilitating liver repair through mechanisms of differentiation and paracrine signaling. Furthermore, it explores the therapeutic potential of exosomes and conditioned media derived from stem cells as biotherapeutic agents in the context of regenerative medicine. By elucidating the mechanisms that underpin liver regeneration, this study aspires to inform the development of effective therapeutic strategies to address liver diseases and slow their progression. By elucidating the underlying mechanisms of liver regeneration, this study aims to contribute to the development of effective therapeutic strategies to address liver diseases and slow their progression.

Freezing sperm for artificial insemination (AI) has been common for decades, but this method causes damage to sperm, which affects its viability and fertility. Various strategies have been used to treat sperm cryopreservation complications, but their results are still not satisfactory. The latest approach in this field is using extracellular vesicles (EVs). The role of EVs in reproduction, such as spermatogenesis, sperm capacitation, and fertility has been proven. EVs can deliver proteins, lipids, nucleic acids, and other molecules to the sperm for repair. The EVs carry proteins, lipids, nucleic acids, and other molecules, which could be involved in sperm quality, functionality or fertility. The application of EV derived from animal and human cell sources for cryoinjury treatment indicates the improvement of sperm quality after freeze-thawing. In addition, different EV engineering methods regarding various EV cargos could be more influential for cryopreserved sperm treatment because they could provide EV customized content for delivering to cryoinjured sperm, according to their unique needs to enhance viability and fertility. In this review, first, we reminded the sperm cryopreservation complications, and next explained the conventional and modern strategies for overcoming them. Then, we have pointed out the role of EV in sperm development and the following mentioned the study results of using EV from different cell sources in sperm cryoinjuries repair. Also, we suggested several predisposing molecules (including microRNAs and proteins) for EV engineering to treat sperm cryopreservation complications by indirect engineering procedure, including genetic manipulation and incubation with therapeutic molecules, and direct engineering procedure, including electroporation, sonication, incubation, saponin permeabilization, extrusion, CaCl2-heat shock, and freeze/thawing. Finally, we discussed the limitations of EV application and ethical considerations in this context. In the meantime, despite these limitations, we pointed out the promising potential of the EV engineering strategies to reduce infertility rates by helping to overcome sperm cryopreservation challenges.

Lung cancer (LC) signifies the primary cause of cancer-related mortality, representing 24 % of all cancer fatalities. LC is intricate and necessitates innovative approaches for early detection, precise diagnosis, and tailored treatment. Exosomes (EXOs), a subclass of extracellular vesicles (EVs), are integral to LC advancement, intercellular communication, tumor spread, and resistance to anticancer therapies. EXOs represent a viable drug delivery strategy owing to their distinctive biological characteristics, such as natural origin, biocompatibility, stability in blood circulation, minimal immunogenicity, and potential for modification. They can function as vehicles for targeted pharmaceuticals and facilitate the advancement of targeted therapeutics. EXOs are pivotal in the metastatic cascade, facilitating communication between cancer cells and augmenting their invasive capacity. Nonetheless, obstacles such as enhancing cargo loading efficiency, addressing homogeneity concerns during preparation, and facilitating large-scale clinical translation persist. Interdisciplinary collaboration in research is crucial for enhancing the efficacy of EXOs drug delivery systems. This review explores the role of EXOs in LC, their potential as therapeutic agents, and challenges in their development, aiming to advance targeted treatments. Future research should concentrate on engineering optimization and developing innovative EXOs to improve flexibility and effectiveness in clinical applications.

In the cardiovascular system, different types of cardiovascular cells can secrete specific exosomes and participate in the maintenance of cardiovascular function and the occurrence and development of diseases. Exosomes carry biologically active substances such as proteins and nucleic acids from cells of origin and can be used as biomarkers for disease diagnosis and prognosis assessment. In addition, exosome-mediated intercellular communication plays a key role in the occurrence and development of cardiovascular diseases and has become a potential therapeutic target. This article emphasizes the importance of understanding the mechanism of exosomes in cardiovascular diseases and systematically details the current understanding of exosomes as regulators of intercellular communication in cardiomyocytes, providing a basis for future research and therapeutic intervention.

Breast cancer remains the leading cause of female mortality worldwide, necessitating innovative and multifaceted approaches to address its various subtypes. Nanotechnology has attracted considerable attention due to its nanoscale dimensions, diverse carrier types, suitability for hydrophobic drug delivery, and capacity for controlled and targeted administration. Nano-sized particles have become prevalent carriers for therapeutic agents targeting breast cancer, thanks to their reproducible synthesis and adjustable properties, including size, shape, and surface characteristics. In addition, certain nanoparticles can enhance therapeutic effects synergistically. However, the immune system often detects and removes these nanoparticles, limiting their efficacy. As a promising alternative, cell membrane-based delivery systems have gained attention due to their biocompatibility and targeting specificity. These membrane-coated drug delivery systems are derived from various cell sources, including blood cells, cancer cells, and stem cells. Leveraging the unique properties of these cell membranes enables precise targeting of breast cancer tumors and associated biomarkers. Inspired by natural structures, cell membranes disguise nanoparticles in the bloodstream, enhancing their retention time in vivo and improving tumor targeting. Consequently, cell membrane-derived nanoparticles (CMDNPs) have been investigated for their potential applications in breast cancer diagnostics, photothermal therapy (PTT), and vaccine development. This review comprehensively explores the potential and limitations of cell membrane-derived drug delivery systems in clinical applications against breast cancer.

Aging is a multifaceted biological process marked by a gradual decline in physiological functions, driven by cellular senescence, oxidative stress, chronic inflammation, and stem cell exhaustion. Extracellular vesicles (EVs), naturally occurring nanoscale vesicles secreted by various cell types, have gained attention as potential therapeutic agents due to their ability to mediate intercellular communication by delivering bioactive molecules, including proteins, lipids, and RNAs. This review provides a comprehensive overview of EV biogenesis, cargo composition, and their mechanistic roles in counteracting aging processes. EVs from diverse sources-such as mesenchymal stem cells, embryonic stem cells, dermal fibroblasts, and colostrum-exhibit regenerative properties by modulating immune responses, enhancing tissue repair, and promoting extracellular matrix homeostasis. Recent preclinical and clinical studies further highlight their potential in addressing age-related diseases and skin rejuvenation. However, significant challenges remain, including standardization of EV production, large-scale manufacturing, safety profiling, and regulatory approval. By leveraging advancements in EV engineering, targeted delivery systems, and combination strategies with existing anti-aging interventions, EV-based therapies hold promise as next-generation approaches in regenerative medicine and longevity enhancement.

Background/Objectives: Exosomes, nanosized vesicles secreted by diverse cell types, have emerged as critical mediators of intercellular communication, tissue repair, and disease pathogenesis. Their roles in dermatology are increasingly recognized, influencing skin health and the progression of various dermatological conditions. This review aims to explore the biogenesis, composition, and mechanisms of exosome uptake in skin cells and their implications in dermatological research and clinical practice. Methods: A comprehensive review of the existing literature was conducted to elucidate the biological composition of exosomes, their roles in skin homeostasis, and their involvement in processes, such as wound healing, tissue regeneration, and barrier function maintenance. This review also examined the diagnostic and therapeutic potential of exosomes in conditions such as psoriasis, eczema, acne, and skin cancer. Results: Exosomes were found to contain intricate compositions, including proteins, lipids, nucleic acids, and bioactive molecules, crucial for maintaining skin homeostasis. They demonstrated significant roles in modulating wound healing and skin regeneration. Emerging evidence highlights their involvement in dermatological conditions and their potential as diagnostic biomarkers and therapeutic agents. Exosome-based approaches hold promise for advancing disease management, although challenges remain in translating these findings into clinical applications. Conclusions: Exosomes represent a promising frontier in dermatology, with the potential to revolutionize the understanding, diagnosis, and treatment of skin-related disorders. Despite the challenges, their complexity and versatility underscore their potential in developing personalized skin health strategies. Further research is warranted to address the existing gaps and harness the full therapeutic potential of exosomes in dermatological applications.

Liquid-liquid phase separation (LLPS) is a significant reversible and dynamic process in organisms. Cells form droplets that are distinct from membrane-bound cell organelles by phase separation to keep biochemical processes in order. Nevertheless, the pathological state of LLPS contributes to the progression of a variety of tumor-related pathogenic issues. Sarcoma is one kind of highly malignant tumor characterized by aggressive metastatic potential and resistance to conventional therapeutic agents. Despite the significant clinical relevance, research on phase separation in sarcomas currently faces several major challenges. These include the limited availability of sarcoma samples, insufficient attention from the research community, and the complex genetic heterogeneity of sarcomas. Recently, emerging evidence have elaborated the specific effects and pathways of phase separation on different sarcoma subtypes, including the effect of sarcoma fusion proteins and other physicochemical factors on phase separation. This review aims to summarize the multiple roles of phase separation in sarcoma and novel molecular inhibitors that target phase separation. These insights will broaden the understanding of the mechanisms concerning sarcoma and offer new perspectives for future therapeutic strategies.

Skin diseases are a broad category of diseases and each has complex conditions, which makes it challenging for dermatologists to provide targeted treatment. Exosomes are natural vesicles secreted by cells and play a key role in cell communication. Due to their unique characteristics, including inherent stability, minimal immunogenicity, high biocompatibility, and exceptional ability to penetrate cells, exosomes are being explored as potential delivery vehicles for therapeutics across various diseases including skin problems. Utilizing exosomes for drug delivery in skin diseases can improve treatment outcomes and reduce the side effects of traditional drug delivery methods. Indeed, exosomes can be engineered or utilized as an innovative approach to deliver therapeutic agents such as small molecule drugs, genes, or proteins specifically to affected skin cells. In addition to targeting specific skin cells or tissues, these engineered exosome-based nanocarriers can reduce off-target effects and improve drug efficacy. Hence, this article highlights the transformative potential of this technology in revolutionizing drug delivery in dermatology and improving patient outcomes.

TDP-43 protein is an RNA-binding protein linked to amyotrophic lateral sclerosis, frontotemporal dementia, and Alzheimer disease. While normally a protein that shuttles between the nucleus and cytoplasm, TDP-43 has recently been found also in extracellular vesicles. These are an important medium for cell-cell communication that allows the transfer of lipids, proteins, and genetic material among cells. An increasing concern in neurodegenerative diseases, however, is the possibility that extracellular vesicles can also provide an effective way to spread misfolded proteins that could "infect" other cells according to a "prion-like" mechanism. To characterize the interaction of TDP-43 with lipid membranes, we carried out a systematic biophysical study using a TDP-43 fragment lacking the first 84 N-terminal residues, called M85, and synthetic model phospholipid membranes. We utilized standard techniques, such as fluorescence and microscopy, complemented by neutron reflectivity measurements. Our results show that lipid charge affects the modality by which M85 interacts with membranes: a higher negative charge induces the protein to bind to the bilayer surface, promoting protein aggregation and decreasing lipid bilayer damage that this interaction causes. Thus, we speculate that the M85-lipid membrane interaction could play an important and previously undefined role in TDP-43-related neurodegenerative diseases.

This study introduces a comprehensive approach to enhancing SiNx nanofilters for exosome isolation from bovine milk using the electrophoretic oscillation-assisted tangent-flow ultrafiltration (EPOTF) process. Reinforcing the nanofilter with electro-spun poly(vinylidene fluoride) (PVDF) fibers significantly improved durability under high-pressure conditions, withstanding nearly 2.8 times greater pressures than nonreinforced nanofilters. The PVDF-fiber-coated nanofilters achieved a flow rate of over 70 mL min-1, compared to just 25 mL min-1 for nonreinforced nanofilters. A filter housing system with copper electrodes isolated from the solution flow path further enhanced the electrical stability of the entire system, widening the EPO voltage range while reducing the risk of corrosion and contamination. The PVDF-fiber-coated nanofilter with the electrode in a separated housing efficiently prevented clogging and bioparticle agglomeration, maintaining constant filtration performance across various voltages and duty cycles. Biochemical analyses confirmed the high concentration and structural integrity of exosomes isolated at high flow rates. Long-term tests verified the superior performance of PVDF-coated filters, successfully filtering 3400 mL of milk over 24 h. These results demonstrate the potential of these advances for highly efficient exosome isolation while maintaining the integrity and shape of exosomes, offering promise for the future of exosome isolation research.

Exosomes are vesicles secreted by cells, typically ranging from 30 to 150 nm in diameter, and serve as crucial mediators of intercellular communication. Exosomes are capable of loading various therapeutic substances, such as small molecule compounds, proteins, and oligonucleotides, thereby making them an ideal vehicle for drug delivery. The distinctive biocompatibility, high stability, and targeting properties of exosomes render them highly valuable for future treatments of diseases like cancer and cardiovascular diseases. Despite the potential advantage of exosomes in delivering biologically active molecules, the techniques for the preparation, purification, preservation, and other aspects of stem cell exosomes are not yet mature enough. In this paper, we briefly introduce the composition, biogenesis, and benefits of exosomes, and primarily focus on summarizing the isolation and purification methods of exosomes, the preparation of engineered exosomes, and their clinical applications, to better provide new ideas for the development of exosome drug delivery systems.

Brain cancer remains a significant challenge in the field of oncology, primarily because of its aggressive nature and the limited treatment options available. Conventional therapies often fall short in effectively targeting tumor cells, while sparing healthy brain tissue from collateral damage. However, exosomes are now recognized as promising nanocarriers for targeted drug delivery. These naturally occurring extracellular vesicles can cross the blood-brain barrier and selectively interact with cancer cells. Utilizing exosomes as drug delivery vehicles offers a novel approach with significant potential for targeted therapy. By encapsulating therapeutic agents within exosomes, drugs can be specifically targeted to tumor cells, maximizing their impact whilst minimizing damage to healthy brain tissue. Furthermore, exosomes can be modified to display molecules that specifically recognize and bind to cancer cells, further enhancing their precision and efficacy. While exosome-based therapies show potential, scalability, purification, and clinical application challenges remain. The scalability of exosome production, purification, and modification techniques remains a hurdle that must be overcome for clinical translation. Additionally, the intricate interactions between the tumor microenvironment and exosomes necessitate further research to optimize therapeutic outcomes. The review explores applications and future perspectives of exosome-based therapies in advancing targeted brain cancer treatment.

Radiotherapy, a widely employed cancer treatment, often triggers diverse inflammatory responses such as radiation enteritis, pulmonary injury, pelvic inflammation, dermatitis, and osteitis. Dietary polyphenols have recently emerged as promising agents for mitigating radiation-induced inflammation. However, their clinical application faced challenges related to variable bioavailability, individual pharmacokinetics, optimal dosing, and limited clinical evidence. Current researches revealed the efficacy of bioactive small molecule polyphenols in addressing radiation-induced inflammation. In this review, along with a comprehensive examination of the etiology and categories of radiation-induced inflammatory conditions, the diversity of polyphenols and elucidating their anti-inflammatory mechanisms are explored. This study emphasizes the recent progresses in delivery systems for dietary polyphenols, aiming to enhance radioprotection effects. The optimized utilization of polyphenols, with a theoretical framework and reference guide, is of paramount relevance. Through diverse delivery mechanisms, the more effective and safer radioprotective strategies become achievable. This endeavor aspires to contribute to breakthroughs in the dietary polyphenols' application, significantly enhancing human health protection during radiotherapy. These comprehensive insights presented here also support (pre)-clinical practices in navigating the complexities of utilizing dietary polyphenols for radioprotection, fostering advancements in the field and improving patient outcomes.

Plant-based extracellular vesicles (PBEVs) have been recognized for their wide range of applications in drug delivery however, the extent of their medicinal applicability depends on how well they are preserved and stored. Assessing their physicochemical properties, such as size, particle concentration, shape, and the activity of their cargo, forms the foundation for determining their stability during storage. Moreover, the evaluation of PBEVs is essential to ensure both safety and efficacy, which are critical for advancing their clinical development. Maintaining the biological activity of EVs during storage is a challenging task, similar to the preservation of cells and other cell-derived products like proteins. However, despite limited studies, it is expected that storing drug-loaded EVs may present fewer challenges compared to cell-based therapies, although some limitations are inevitable. This article provides a comprehensive overview of current knowledge on PBEVs preservation and storage methods, particularly focusing on their role as drug carriers. PBEVs hold promise as potential candidates for oral drug administration due to their effective intestinal absorption and ability to withstand both basic and acidic environments. However, maintaining their preservation and stability during storage is critical. Moreover, this review centers on the isolation, characterization, and storage of PBEVs, exploring the potential advantages they offer. Furthermore, it highlights key areas that require further research to overcome existing challenges and enhance the development of effective preservation and storage methods for therapeutic EVs.

Extracellular vesicles (EVs) have been explored as promising vehicles for drug delivery. One of the most valuable features of EVs is their ability to cross physiological barriers, particularly the blood-brain barrier (BBB). This significantly enhances the development of EV-based drug delivery systems for the treatment of CNS disorders. The present review focuses on the factors and techniques that contribute to the successful delivery of EV-based therapeutics to the brain. Here, we discuss the major methods of brain targeting which includes the utilization of different administration routes, capitalizing on the biological origins of EVs, and the modification of EVs through the addition of specific ligands on to the surface of EVs. Finally, we discuss the current challenges in large-scale EV production and drug loading while highlighting future perspectives regarding the application of EV-based therapeutics for brain delivery.

Exosomes are microscopic vesicles released by cells that transport various biological materials and play a vital role in intercellular communication. When they are engineered, they serve as efficient delivery systems for therapeutic agents, making it possible to precisely deliver active pharmaceutical ingredients to organs, tissues, and cells. Exosomes' pharmacokinetics, or how they are transported and metabolized inside the body, is affected by several factors, including their source of origination and the proteins in their cell membranes. The pharmacokinetics and mobility of both native and modified exosomes are being observed in living organisms using advanced imaging modalities such as in vitro-in vivo simulation, magnetic resonance imaging, and positron emission tomography. Establishing comprehensive criteria for the investigation of exosomal pharmacokinetic is essential, given its increasing significance in both therapy and diagnostics. To obtain a thorough understanding of exosome intake, distribution, metabolism, and excretion, molecular imaging methods are crucial. The development of industrial processes and therapeutic applications depends on the precise measurement of exosome concentration in biological samples. To ensure a seamless incorporation of exosomes into clinical practice, as their role in therapeutics grows, it is imperative to conduct a complete assessment of their pharmacokinetics. This review provides a brief on how exosome-based research is evolving and the need for pharmacokinetic consideration to realize the full potential of these promising new therapeutic approaches.

In the recent decade, extracellular vesicles (EVs) have been released from nearly all the kingdoms, modulating intercellular communication and maintaining the human body's homeostasis by regulating different cellular processes. Among EVs, exosomes are the emerging field in biopharmaceuticals. They have lipid bilayer ranging from 30 to 150 nm in size and encompass DNA, RNA, protein lipids, etc. Their sources are widespread, easy to acquire, and cost-effective in manufacturing. This review focuses on the detailed classification of exosomes existing in nature, knowledge and application of omics, therapeutic, diagnostic and theranostic application of exosomes. It covers diseases such as cancer, infectious diseases (viral, bacterial, fungal infections), neurodegenerative diseases, metabolic diseases, lifestyle diseases (diabetes, cardiovascular, gastric disorder (IBD)), autoimmune disorders and their biodistribution. This article unfolds the recent progress in the exosomes arena and covers all the regulatory considerations (FDA, EMA, and other nations) involved with it. Moreover, a detailed discussion about clinical trials and its manifestation with exosomes and challenges associated with their isolation procedures, reproducibility, and safety concerns.

Degenerative joint disease, known as osteoarthritis (OA), is characterized by pain, swelling, and decreased mobility. The illness has a major negative influence on patients' quality of life and is common around the world, especially among older people. Nevertheless, there are insufficient possibilities for early diagnosis and therapy. Extracellular vesicles, or EVs, control the immune response, tissue healing, and cellular communication.

This work offers a bibliometric representation of the areas of focus and correlations between extracellular vesicles and osteoarthritis. We searched for osteoarthritis and extracellular vesicles in publications in the Web of Science Core Collection (WoSCC) database. Bibliometrics, an R package, CiteSpace 6.1. R2, and VOSviewer 1.6.17 were used to perform bibliometric analyses of concentration fields, trends, and relevant factors.

944 papers from 59 nations were published; the countries that contributed the most to the field were China, the USA, and Italy. Professors Laura and Enrico are the top contributors. Sichuan University, Istituto Ortopedico Galeazzi, and Shanghai Jiao Tong University are the top three universities. The International Journal of Molecular Sciences is an excellent publication. Exosome, expression, knee osteoarthritis, extracellular vesicle, mesenchymal stem cell, osteoarthritis, and inflammation are the most often occurring keywords.

These results suggest areas of interest and focus for future research on EVs and OA. This trend suggests that the volume of literature on OA and EVs will continue to rise, with more research being published in the future. This study helps scholars understand current research hotspots in the field and may inspire future research.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with impaired cognitive function and memory loss. Currently, available therapeutics can effectively alleviate the symptoms of AD, but there is a lack of treatment to halt the progression of the disease. In recent years, exosomes have gained much attention due to their involvement in various neurological disorders. Exosomes are small extracellular vesicles comprising lipids, proteins, DNA, non-coding RNA, and mRNAs, can carry various therapeutic molecules, and are potential drug delivery vehicles. Exosomes are known as a double-edged sword due to their involvement in both the pathogenesis and management of AD. This review explores the function of exosomes in the pathophysiology, treatment, and diagnosis of AD, also emphasizing their potential as a targeted drug delivery carrier to the brain. This review seeks to provide novel perspectives to understand better the onset, targeted treatment, and diagnosis of AD using exosomes.

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are nanoscale lipid bilayer vesicles secreted by mesenchymal stem cells. They inherit the parent cell's attributes, facilitating tissue repair and regeneration, promoting angiogenesis, and modulating the immune response, while offering advantages like reduced immunogenicity, straightforward administration, and enhanced stability for long-term storage. These characteristics elevate MSC-EVs as highly promising in cell-free therapy with notable clinical potential. It is critical to delve into their pharmacokinetics and thoroughly elucidate their intracellular and in vivo trajectories. A detailed summary and evaluation of existing tracing strategies are needed to establish standardized protocols. Here, we have summarized and anticipated the research progress of MSC-EVs in various biomedical imaging techniques, including fluorescence imaging, bioluminescence imaging, nuclear imaging (PET, SPECT), tomographic imaging (CT, MRI), and photoacoustic imaging. The challenges and prospects of MSC-EV tracing strategies, with particular emphasis on clinical translation, have been analyzed, with promising solutions proposed.

Traditional drug therapies suffer from problems such as easy drug degradation, side effects, and treatment resistance. Traditional disease diagnosis also suffers from high error rates and late diagnosis. Extracellular vesicles (EVs) are nanoscale spherical lipid bilayer vesicles secreted by cells that carry various biologically active components and are integral to intercellular communication. EVs can be found in different body fluids and may reflect the state of the parental cells, making them ideal noninvasive biomarkers for disease-specific diagnosis. The multifaceted characteristics of EVs render them optimal candidates for drug delivery vehicles, with evidence suggesting their efficacy in the treatment of various ailments. However, poor stability and easy degradation of natural EVs have affected their applications. To solve the problems of poor stability and easy degradation of natural EVs, they can be engineered and modified to obtain more stable and multifunctional EVs. In this study, we review the shortcomings of traditional drug delivery methods and describe how to modify EVs to form engineered EVs to improve their utilization. An innovative stimulus-responsive drug delivery system for EVs has also been proposed. We also summarize the current applications and research status of EVs in the diagnosis and treatment of different systemic diseases, and look forward to future research directions, providing research ideas for scholars.

Exosomes, which are nano-sized natural vesicles secreted by cells, are crucial for intercellular communication and interactions, playing a significant role in various physiological and pathological processes. Their characteristics, such as low toxicity and immunogenicity, high biocompatibility, and remarkable drug delivery capabilities-particularly their capacity to traverse the blood-brain barrier-make exosomes highly promising vehicles for drug administration in the treatment of brain disorders. This review provides a comprehensive overview of exosome biogenesis and isolation techniques, strategies for the drug loading and functionalization of exosomes, and exosome-mediated blood-brain barrier penetration mechanisms, with a particular emphasis on recent advances in exosome-based drug delivery for brain disorders. Finally, we address the opportunities and challenges associated with utilizing exosomes as a drug delivery system for the brain, summarizing the barriers to clinical translation and proposing future research directions.

Extracellular vesicles (EVs) are membrane vesicles secreted by all types of cells, including bacteria, animals, and plants. These vesicles contain proteins, nucleic acids, and lipids from their parent cells and can transfer these components between cells. EVs have attracted attention for their potential use in diagnosis and therapy due to their natural properties, such as low immunogenicity, high biocompatibility, and ability to cross the blood-brain barrier. They can also be engineered to carry therapeutic molecules. EVs can be delivered via various routes. The intranasal route is particularly advantageous for delivering them to the central nervous system, making it a promising approach for treating neurological disorders.

This review delves into the promising potential of intranasally administered EVs-based therapies for various medical conditions, with a particular focus on those affecting the brain and central nervous system. Additionally, the potential use of these therapies for pulmonary conditions, cancer, and allergies is examined, offering a hopeful outlook for the future of medical treatments.

The intranasal administration of EVs offers significant advantages over other delivery methods. By directly delivering EVs to the brain, specifically targeting areas that have been injured, this administration proves to be highly efficient and effective, providing reassurance about the progress in medical treatments. Intranasal delivery is not limited to brain-related conditions. It can also benefit other organs like the lungs and stimulate a mucosal immune response against various pathogens due to the highly vascularized nature of the nasal cavity and airways. Moreover, it has the added benefit of minimizing toxicity to non-targeted organs and allows the EVs to remain longer in the body. As a result, there is a growing emphasis on conducting clinical trials for intranasal administration of EVs, particularly in treating respiratory tract pathologies such as coronavirus disease.

The intercellular communication role of extracellular vesicles has been widely proved in various organisms. Compelling evidence has illustrated the involvement of these vesicles in both physiological and pathological processes. Various studies indicate that extracellular vesicles surpass conventional synthetic drug carriers, owing to their abundance in organisms, enhanced targeting ability and low immunogenicity. Therefore, extracellular vesicles have been deemed to be potential drug carriers for the treatment of various diseases, and related studies have increased rapidly. Here, we intend to provide a comprehensive and in-depth review of recent advances in the sources, delivery function, extraction and cargo-loading technologies of extracellular vesicles, as well as their clinical potential in constructing emerging nanomedicine therapeutic platforms. In particular, microfluidic-based isolation and drug-loading technologies, as well as the treatment of various diseases, are highlighted. We also make comparisons between extracellular vesicles and other conventional drug carriers and discuss the challenges in developing drug delivery platforms for clinical translation.

Among the emerging strategies for cancer theranostics, nanomedicines offer significant promise in advancing both patients' diagnosis and treatment. In combination with nanobodies, nanomedicines can potentially enhance the precision and efficiency of drug or imaging agent delivery, addressing key limitations of current approaches, such as off-target toxicities. The development of nanomedicines will be further accelerated by the creation of smart nanoparticles, and their integration with immunotherapy. Obviously, the success of nano-immunotherapy will depend on a comprehensive understanding of the tumor microenvironment, including the complex interplay of mechanisms that drive cancer-mediated immunosuppression and immune escape. Hence, effective therapeutic targeting of the tumor microenvironment requires modulation of immune cell function, overcoming resistance mechanisms associated with stromal components or the extracellular matrix, and/or direct elimination of cancer cells. Identifying key molecules involved in cancer progression and drug resistance is, therefore, essential for developing effective therapies and diagnostic tools that can predict patient responses to treatment and monitor therapeutic outcomes. Current nanomedicines are being designed with careful consideration of factors such as the choice of carrier (e.g., biocompatibility, controlled cargo release) and targeting moiety. The unique properties of nanobodies make them an effective engineering tool to target biological molecules with high affinity and specificity. In this review, we focus on the latest applications of nanobodies for targeting various components of the tumor microenvironment for diagnostic and therapeutic purposes. We also explore the main types of nanoparticles used as a carrier for cancer immunotherapies, as well as the strategies for formulating nanoparticle-nanobody conjugates. Finally, we highlight how nanobody-nanoparticle formulations can enhance current nanomedicines.

Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs). Consequently, using MSC-EVs emerged as a pioneering strategy to mitigate the risks related to cell therapy while providing MSC therapeutic benefits. Despite the promises given by MSC- and MSC-EV-based approaches, many improvements are considered to optimize the therapeutic significance of these therapies. This review aspires to provide a comprehensive and detailed overview of current knowledge on corneal therapies involving MSCs and MSC-EVs, the strategies currently under evaluation, and the gaps remaining to be addressed for clinical implementation. From encapsulating MSCs or their EVs into biomaterials to enhance the ocular retention time to loading MSC-EVs with therapeutic drugs, a wide range of ground-breaking strategies are currently contemplated to lead to the safest and most effective treatments. Promising research initiatives also include diverse gene therapies and the targeting of specific cell types through the modification of the EV surface, paving the way for future therapeutic innovations. As one of the most important challenges, MSC-EV large-scale production strategies are extensively investigated and offer a wide array of possibilities to meet the needs of clinical applications.

Plant-derived extracellular vesicles (EVs) are natural nanovesicles for drug delivery. This study isolated and characterised EVs from medicinal plants as delivery vehicles.

Precipitation method was employed for the isolation and characterised using DLS, SEM, and TEM. The encapsulation efficiency (EE) and antioxidant activity of ascorbic acid (AA)-EVs were evaluated.

The total yields of lyophilised vesicles per weight of the sample were 6.0, 8.6 and 9.2 mg/g for garlic, turmeric and ginger, respectively. Mean size of garlic-derived EVs, ginger-derived EVs, and turmeric-derived EVs were 101.0 ± 6.7, 226.4 ± 62.2 and 90.7 ± 2.5 nm, respectively. The zeta potential of the EVs was between -33.2 ± 10.9 and -28.8 ± 8.43 mV. Spherical morphology of the nanovesicles was confirmed by SEM and TEM. The EE of the EVs was between 78.1 ± 2.8% and 87.2 ± 1.4%.

Overall, the antioxidant activity of AA-loaded EVs was better compared to free AA. This study provides evidence that these medicinal plants are rich sources for developing nanotherapeutics.

The metabolic enzyme ATP citrate lyase is overexpressed in several cancers and links glucose metabolism with de novo fatty acid synthesis pathway by catalyzing the conversion of citrate into acetyl CoA and oxaloacetate. Potassium hydroxycitrate, its natural inhibitor, exhibits anticancer activity; however, its use is limited due to low bioavailability. This study aims to improve the efficacy of hydroxycitrate by its encapsulation in bovine milk exosome surface conjugated with folate for targeting lung cancer cells. The mean particle size of potassium hydroxycitrate-loaded exosomes (Exo-KH) and paclitaxel exosomes (Exo-Pac) was 183 nm and 174 nm; they had spherical morphology and encapsulation efficiency of 16.87 ± 2.78% and 27.65 ± 3.23%, respectively. In the in vitro study, Exo-KH suppressed the proliferation of A549 cells and significantly reduced ACLY mRNA expression. In addition to ACLY, EXO-KH also downregulated the mRNA expression of other crucial metabolic enzymes such as fatty acid synthase and isocitrate dehydrogenase 1. EXO-KH formulation caused significant increase in apoptosis rate (< 75%) and reactive oxygen species production and reduced ACLY protein expression in A549 cells. Moreover, the pharmacokinetic study revealed the sustained release of hydroxycitrate (half-life 22.74 h and clearance 0.13 µg/ml) from the exoformulation. Altogether, the study findings highlight the beneficial role of EXO-KH formulation against lung cancer.

Exosomes have emerged as promising tools for targeted drug delivery in biomedical applications and medicine. This review delves into the scientific advancements, challenges, and future prospects specifically associated with these technologies. In this work, we trace the research milestones that led to the discovery and characterization of exosomes and extracellular vesicles, and discuss strategies for optimizing the synthetic yield and the loading of these particles with various therapeutics. In addition, we report the current major issues affecting the field and hampering the clinical translation of these technologies. Highlighting the pivotal role of imaging techniques, we explore how they drive exosome therapy and development by offering insights into biodistribution and cellular trafficking dynamics. Methodologies for vesicle isolation, characterization, loading, and delivery mechanisms are thoroughly examined, alongside strategies aimed at enhancing their therapeutic efficacy. Special emphasis was dedicated to their therapeutic properties, particularly to their ability to deliver biologics into the cytoplasm. Furthermore, we delve into the intricate balance between surface modifications and targeting properties including also transgenic methods aimed at their functionalization and visualization within biological systems. This review underscores the transformative potential of these carriers in targeted drug delivery and identifies crucial areas for further research and clinical translation.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. The primary objective of this study was to assess the therapeutic potential of puerarin loaded bone marrow mesenchymal stem cell-derived exosomes (Pue@BMSC-Exo), and reveal their inflammatory regulating mechanisms through affecting the nuclear factor kappa-B (NF-κB) signaling pathway. In this study, exosomes derived from BMSCs were isolated and identified. Cell proliferation and migration were evaluated by CCK-8 and scratch methods. Furthermore, histological and micro-computed tomography analysis were performed to assess alterations of articular cartilage in OA rats. Results showed that BMSC-Exo and Pue@BMSC-Exo conformed with the basic characteristics of exosomes. BMSC-Exo increased the solubility of Pue and enhanced drug uptake by chondrocytes. In addition, Pue@BMSC-Exo stimulated proliferation and migration of chondrocyte, and also promoted cartilage repair by reducing matrix metalloproteinase MMP13 production and increasing type II collagen (Col2) synthesis. Furthermore, Pue@BMSC-Exo, by effectively inhibiting the NF-κB signaling pathway, reduced the production of inflammatory mediators and attenuated the release of the inflammatory marker nitric oxide (NO), ultimately ameliorating the damage of chondrocyte. These findings exhibited the potential therapeutic significance of Pue@BMSC-Exo in OA and warranted further exploration in clinical applications.

Extracellular vesicles (EVs) are membrane-bound entities secreted by each cell, categorized as, exosomes, microvesicles or apoptotic bodies based on their size and biogenesis. They serve as promising vectors for drug delivery due to their capacity to carry diverse molecular signatures reflective of their cell of origin. EV research has significantly advanced since their serendipitous discovery, with recent studies focusing on their roles in various diseases and their potential for targeted therapy. In liver diseases, EVs are particularly promising for precision medicine, providing diagnostic and therapeutic potential in conditions such as metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, hepatocellular carcinoma, alcoholic liver disease, liver fibrosis, and acute liver failure. Despite challenges in isolation and characterization, engineered EVs have shown efficacy in delivering therapeutic agents with improved targeting and reduced side effects. As research progresses, EVs hold great promise to revolutionize precision medicine in liver diseases, offering targeted, efficient, and versatile therapeutic options. In this review, we summarize various techniques for loading EVs with therapeutic cargo including both passive and active methods, and the potential of bioengineered EVs loaded with various molecules, such as miRNAs, proteins, and anti-inflammatory drugs in ameliorating clinical pathologies of liver diseases.

Extracellular vesicles (EVs) are secreted by almost all cell types and contain DNA, RNA, proteins, lipids and other metabolites. EVs were initially believed to be cellular waste but now recognized for their role in cell-to-cell communication. Later, EVs from immune cells were discovered to function similarly to their parent cells, paving the way for their use as gene and drug carriers. EVs from different cell types or biological fluids carry distinct cargo depending on their origin, and they perform diverse functions. For instance, EVs derived from stem cells possess pluripotent properties, reflecting the cargo from their parent cells. Over the past two decades, substantial preclinical and clinical research has explored EVs-mediated drug and gene delivery to various organs, including the brain. Natural or intrinsic EVs may be effective for certain applications, but as drug or gene carriers, they demonstrate broader and more efficient potential across various diseases. Here, we review research on using EVs to treat central nervous system (CNS) diseases, such as Alzheimer's Disease, Parkinson diseases, depression, anxiety, dementia, and acute ischemic strokes. We first reviewed the naïve EVs, especially mesenchymal stem cell (MSC) derived EVs in CNS diseases and summarized the clinical trials of EVs in treating CNS diseases and highlighted the reports of two complete trials. Then, we overviewed the preclinical research of EVs as drug and gene delivery vehicles in CNS disease models, including the most recent two years' progress and discussed the mechanisms and new methods of engineered EVs for targeting CNS. Finally, we discussed challenges and future directions and of EVs as personalized medicine for CNS diseases.

Cancer, a significant cause of mortality, necessitates improved drug delivery strategies. Exosomes, as natural drug carriers, offer a more efficient, targeted, and less toxic drug delivery system compared to direct dispersal methods via ingestion or injection. To be successfully implemented as drug carriers, efficient loading of drugs into exosomes is crucial, and a deeper understanding of the loading mechanism remains to be solved. This study introduces surface-enhanced Raman scattering (SERS) to monitor drug loading efficacy at the single vesicle level. By enhancing the Raman signal, SERS overcomes limitations in Raman spectroscopy. A gold nanopyramids array-based SERS substrate assesses exosome heterogeneity in drug-loading capabilities with the help of single-layer graphene for precise quantification. This research advances targeted drug delivery by presenting a more efficient method of evaluating drug-loading efficiency into individual exosomes through SERS-based monitoring. Furthermore, the study explores leveraging osmotic pressure variations, enhancing the efficiency of drug loading into exosomes.

Exosomes have become a potential field of nanotechnology for the treatment and identification of many disorders. However, the generation of exosomes is a difficult, time-consuming, and low-yielding procedure. At the same time, exosome mimetics (EM) resemble exosomes in their characteristics but have higher production yields. The aim of this study was to produce natural killer (NK) cell-derived EM (NKEM) loaded with sorafenib and test their killing ability against thyroid cancer cell lines.

Sorafenib was loaded into NKEM by mixing sorafenib with NK cells during NKEM production (NKEM-S). Then, these two types of nanoparticles were characterized with nanoparticle tracking analysis (NTA) to measure their sizes. In addition, the cellular uptake and in vitro killing effect of NKEM-S on thyroid cancer cell lines were investigated using confocal laser microscopy and bioluminescence imaging (BLI) techniques.

The uptake of NKEM and NKEM-S by the thyroid cancer cells was observed. Moreover, BLI confirmed the killing and anti-proliferation effect of NKEM-S on two thyroid cancer cell lines. Especially important, the NKEM-S demonstrated a desirable killing effect even for anaplastic thyroid cancer (ATC) cells.

Sorafenib-loaded NKEM showed the ability to kill thyroid cancer cells in vitro, even against ATC. This provides a new opportunity for drug delivery systems and thyroid cancer treatment.

The inherent limitations of traditional treatments for Diabetic Retinopathy (DR) have spurred the development of various nanotechnologies, offering a safer and more efficient approach to managing the disease. Nanomedicine platforms present promising advancements in the diagnosis and treatment of DR by enhancing imaging capabilities, enabling targeted and controlled drug delivery. These innovations ultimately lead to more effective and personalized treatments with fewer side effects. This review highlights the progress, challenges, and opportunities in developing effective diagnostics and therapeutics for DR. Additionally, it explores innovative engineering techniques that leverage our growing understanding of nano-bio interactions to create more potent nanotherapeutics for patients.

Over the last few decades: heart disease (HD) has emerged as one of the deadliest diseases in the world. Approximately more than 31 % of the population dies from HD each year. The Diagnosis of HD in an earlier stage is a cognitively challenging task due to the vast and complex availability of medical datasets. Many tests are available for the diagnosis of HD, such as ECG, etc.; but the proper diagnosis of the disease is still a great challenge.

Motivated by existing challenges and the significance of HD, the authors developed a novel hybrid XGBoost Classifier framework for HD prediction that incorporates outlier removal and optimized hyperparameter tuning. In this approach, outliers were handled using z-score and interquartile range (IQR) methods, and hyperparameters were optimized using the "Optuna" framework. Additionally, the impact of different train-test ratios (70,30, 80:20, and 90:10) on model performance was evaluated using Cleveland HD dataset, both with and without outliers.

The proposed hybrid model achieved the finest performance metrics without outliers on a 90:10 train-test ratio with an accuracy of 95.45 %, sensitivity of 92.86 %, precision of 100 %, specificity of 100 %, f1-score 96.3 %, training time 0.8 × 10-16 s and testing time 0.1 × 10-17 s. It was validated by Stratify K-Fold Cross-Validation.

This study highlights the importance of data preprocessing, appropriate train-test ratios, and hyperparameter optimization in HD prediction. The proposed framework provides a promising solution for accurate and efficient HD diagnosis, offering potential benefits for cardiac patient healthcare and decision-making.

Periodontitis is a chronic inflammatory disease that destroys tooth-supporting structures and poses significant public health challenges due to its high prevalence and links to systemic health conditions. Traditional treatments are effective in reducing the inflammatory response and improving the clinical symptoms of periodontitis. However, these methods are challenging to achieve an ideal treatment effect in alveolar bone repair. Mesenchymal stem cells (MSCs) represent a potential alternative for the treatment of periodontal bone defects due to their self-renewal and differentiation capabilities. Recent research indicates that MSCs exert their effects primarily through paracrine mechanisms. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) serve as pivotal mediators in intercellular communication, transferring microRNAs (miRNAs), messenger RNAs (mRNAs), proteins, and cytokines to recipient cells, thereby emulating the therapeutic effects of MSCs. In periodontitis, MSC-EVs play a pivotal role in immunomodulation and bone remodeling, thereby facilitating periodontal bone repair. As a cell-free therapy, MSC-EVs demonstrate considerable clinical potential due to their specialized membrane structure, minimal immunogenicity, low toxicity, high biocompatibility, and nanoscale size. This review indicates that MSC-EVs represent a promising approach for periodontitis treatment, with the potential to overcome the limitations of traditional therapies and offer a more effective solution for bone repair in periodontal disease. In this review, we introduce MSC-EVs, emphasizing their mechanisms and clinical applications in periodontal bone repair. It synthesizes recent advances, existing challenges, and future prospects to present up-to-date information and novel techniques for periodontal regeneration and to guide the improvement of MSC-EV therapy in clinical practice.

Plant-derived extracellular vesicles (PDEVs) are membrane vesicles characterized by a phospholipid bilayer as the basic skeleton that is wrapped by various functional components of proteins and nucleic acids. An increasing number of studies have confirmed that PDEVs can be a potential treatment of inflammatory bowel disease (IBD) and can, to some extent, compensate for the limitations of existing therapies.

This review summarizes the recent advances and potential mechanisms underlying PDEVs obtained from different sources to alleviate IBD. In addition, the review discusses the possible applications and challenges of PDEVs, providing a theoretical basis for exploring novel and practical therapeutic strategies for IBD.

In IBD, the crosstalk mechanism of PDEVs may regulate the intestinal microenvironment homeostasis, especially immune responses, the intestinal barrier, and the gut microbiota. In addition, drug loading enhances the therapeutic potential of PDEVs, particularly regarding improved tissue targeting and stability. In the future, not only immunotherapy based on PDEVs may be an effective treatment for IBD, but also the intestinal barrier and intestinal microbiota will be a new direction for the treatment of IBD.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. As a chronic inflammatory disease with a complicated pathophysiology marked by abnormal lipid metabolism and arterial plaque formation, atherosclerosis is a major contributor to CVDs and can induce abrupt cardiac events. The discovery of exosomes' role in intercellular communication has sparked a great deal of interest in them recently. Exosomes are involved in strategic phases of the onset and development of atherosclerosis because they have been identified to control pathophysiologic pathways including inflammation, angiogenesis, or senescence. This review investigates the potential role of stem cell-derived exosomes in atherosclerosis management. We briefly introduced atherosclerosis and stem cell therapy including stem cell-derived exosomes. The biogenesis of exosomes along with their secretion and isolation have been elaborated. The design engineering of exosomes has been summarized to present how drug loading and surface modification with targeting ligands can improve the therapeutic and targeting capacity of exosomes, demonstrating atheroprotective action. Moreover, the mechanism of action (endothelial dysfunction, reduction of dyslipidemia, macrophage polarization, vascular calcification, and angiogenesis) of drug-loaded exosomes to treat atherosclerosis has been discussed in detail. In the end, a comparative and balanced viewpoint has been given regarding the current challenges and potential solutions to advance exosome engineering for cardiovascular therapeutic applications.